Hartman Institute for Therapeutic Organ Regeneration

Platelet-derived growth factor-AB promotes the generation of adult bone marrow-derived cardiac myocytes.

TitlePlatelet-derived growth factor-AB promotes the generation of adult bone marrow-derived cardiac myocytes.
Publication TypeJournal Article
Year of Publication2004
AuthorsXaymardan M, Tang L, Zagreda L, Pallante B, Zheng J, Chazen JL, Chin A, Duignan I, Nahirney P, Rafii S, Mikawa T, Edelberg JM
JournalCirc Res
Volume94
Issue5
PaginationE39-45
Date Published2004 Mar 19
ISSN1524-4571
KeywordsAnimals, Bone Marrow Cells, Bone Marrow Transplantation, Cell Differentiation, Computer Systems, Exercise Test, Fibroblast Growth Factor 2, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Microscopy, Video, Myocardial Infarction, Myocytes, Cardiac, Platelet-Derived Growth Factor, Rats, Rats, Inbred F344, RNA, Messenger, Ultrasonography, Vascular Endothelial Growth Factor A
Abstract

The directed generation of cardiac myocytes from endogenous stem cells offers the potential for novel therapies for cardiovascular disease. To facilitate the development of such approaches, we sought to identify and exploit the pathways directing the generation of cardiac myocytes from adult rodent bone marrow cells (BMCs). In vitro cultures supporting the spontaneous generation of functional cardiac myocytes from murine BMCs demonstrated induced expression of platelet-derived growth factor (PDGF)-A and -B isoforms with alpha- and beta-myosin heavy chains as well as connexin43. Supplementation of PDGF-AB speeded the kinetics of myocyte development in culture by 2-fold. In a rat heart, myocardial infarction pretreatment model PDGF-AB also promoted the derivation of cardiac myocytes from BMCs, resulting in a significantly greater number of islands of cardiac myocyte bundles within the myocardial infarction scar compared with other treatment groups. However, gap junctions were detected only between the cardiac myocytes receiving BMCs alone, but not BMCs injected with PDGF-AB. Echocardiography and exercise testing revealed that the functional improvement of hearts treated with the combination of BMCs and PDGF-AB was no greater than with injections of BMCs or PDGF-AB alone. These studies demonstrated that PDGF-AB enhances the generation of BMC-derived cardiac myocytes in rodent hearts, but suggest that alterations in cellular patterning may limit the functional benefit from the combined injection of PDGF-AB and BMCs. Strategies based on the synergistic interactions of PDGF-AB and endogenous stem cells will need to maintain cellular patterning in order to promote the restoration of cardiac function after acute coronary occlusion.

DOI10.1161/01.RES.0000122042.51161.B6
Alternate JournalCirc Res
PubMed ID14963008
Grant ListAG19738 / AG / NIA NIH HHS / United States
AG20918 / AG / NIA NIH HHS / United States
HL54128 / HL / NHLBI NIH HHS / United States
HL62175 / HL / NHLBI NIH HHS / United States
HL67150 / HL / NHLBI NIH HHS / United States
HL67839 / HL / NHLBI NIH HHS / United States

Weill Cornell Medicine
Hartman Institute for Therapeutic Organ Regeneration
1300 York Ave, Box 136 New York, NY 10065